Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein

Sarah Lapidus, Feimei Liu, Arnau Casanovas-Massana, Yile Dai, John D. Huck, Carolina Lucas, Jon Klein, Renata B. Filler, Madison S. Strine, Mouhamad Sy, Awa B. Deme, Aida S. Badiane, Baba Dieye, Ibrahima Mbaye Ndiaye, Younous Diedhiou, Amadou Moctar Mbaye, Cheikh Tidiane Diagne, Inés Vigan-Womas, Alassane Mbengue, Bacary D. SadioMoussa M. Diagne, Adam J. Moore, Khadidiatou Mangou, Fatoumata Diallo, Seynabou D. Sene, Mariama N. Pouye, Rokhaya Faye, Babacar Diouf, Nivison Nery, Federico Costa, Mitermayer G. Reis, M. Catherine Muenker, Daniel Z. Hodson, Yannick Mbarga, Ben Z. Katz, Jason R. Andrews, Melissa Campbell, Ariktha Srivathsan, Kathy Kamath, Elisabeth Baum-Jones, Ousmane Faye, Amadou Alpha Sall, Juan Carlos Quintero Vélez, Michael Cappello, Michael Wilson, Choukri Ben-Mamoun, Richard Tedder, Myra McClure, Peter Cherepanov, Fabrice A. Somé, Roch K. Dabiré, Carole Else Eboumbou Moukoko, Jean Bosco Ouédraogo, Yap Boum, John Shon, Daouda Ndiaye, Adam Wisnewski, Sunil Parikh, Akiko Iwasaki, Craig B. Wilen, Albert I. Ko, Aaron M. Ring, Amy K. Bei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.

Original languageEnglish (US)
Article number22175
JournalScientific reports
Issue number1
StatePublished - Dec 2022

ASJC Scopus subject areas

  • General


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